chr15-71469640-G-C

Variant names:

• chr15-71469640-G-C
• rs12913412
• NM_024817.3:c.1152+57817G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024817.3(THSD4):​c.1152+57817G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,104 control chromosomes in the GnomAD database, including 2,551 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2551 hom., cov: 32)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.851
• Publications: 4 publications found

Genes affected

THSD4 (HGNC:25835): (thrombospondin type 1 domain containing 4) Predicted to enable hydrolase activity. Predicted to be an extracellular matrix structural constituent. Predicted to act upstream of or within elastic fiber assembly. Located in collagen-containing extracellular matrix and extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

THSD4 Gene-Disease associations (from GenCC):

• aortic aneurysm, familial thoracic 12

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• familial thoracic aortic aneurysm and aortic dissection

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Franklin by Genoox, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024817.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THSD4	NM_024817.3	MANE Select	c.1152+57817G>C		intron	N/A	NP_079093.2	Q6ZMP0-1
	THSD4	NM_001394532.1		c.1152+57817G>C		intron	N/A	NP_001381461.1	Q6ZMP0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THSD4	ENST00000261862.8	TSL:5 MANE Select	c.1152+57817G>C		intron	N/A	ENSP00000261862.8	Q6ZMP0-1
	THSD4	ENST00000355327.7	TSL:5	c.1152+57817G>C		intron	N/A	ENSP00000347484.3	Q6ZMP0-1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25974 AN: 151986 Hom.: 2555 Cov.: 32

Gnomad AFR AF: 0.0833

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.181

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.171 AC: 25989 AN: 152104 Hom.: 2551 Cov.: 32 AF XY: 0.173 AC XY: 12829 AN XY: 74340

African (AFR) AF: 0.0836 AC: 3469 AN: 41518

American (AMR) AF: 0.179 AC: 2733 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 584 AN: 3470

East Asian (EAS) AF: 0.301 AC: 1544 AN: 5138

South Asian (SAS) AF: 0.307 AC: 1478 AN: 4816

European-Finnish (FIN) AF: 0.179 AC: 1893 AN: 10572

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13511 AN: 67984

Other (OTH) AF: 0.180 AC: 380 AN: 2112

Alfa AF: 0.0928 Hom.: 142

Bravo AF: 0.168

Asia WGS AF: 0.307 AC: 1067 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.088
DANN	Benign	0.56
PhyloP100		-0.85
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12913412; hg19: chr15-71761979;